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Pinometostat (EPZ5676) DOT1L inhibitor

Name: Pinometostat (EPZ5676)
Brand: Selleck Chemicals
SKU: S7062
Availability: InStock
Rating: 5 (56 reviews)

Cat.No.S7062

Pinometostat (EPZ5676) is an S-adenosyl methionine (SAM) competitive inhibitor of protein methyltransferase DOT1L with K_i of 80 pM in a cell-free assay, demonstrating >37,000-fold selectivity against all other PMTs tested, inhibits H3K79 methylation in tumor. Phase 1.

Chemical Structure

Molecular Weight: 562.71

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.99%

99.99

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Related Targets	Epigenetic Reader Domain HDAC JAK AMPK PKC PARP HIF Histone Acetyltransferase Aurora Kinase Sirtuin PRMT Histone Demethylase EZH1/2 DNA Methyltransferase Pim LSD1 MLL JMJD G9a/GLP NSD FTO MicroRNA PAD SETD SMYD DOT1 COMT WDR5 HNMT SAM MTase
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Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
MV4-11	Function assay	4 days	Inhibition of DOT1L in human MV4-11 cells expressing MLL-AF4 assessed as reduction of H3K79me2 level after 4 days by ELISA method	25406853
MOLM13	Proliferation assay		Antiproliferative activity against human MOLM13 cells containing MLL-AF9, EC50=4 nM	23879463
MV4-11	Proliferation assay		Antiproliferative activity against human MV4-11 cells containing MLL-AF4, EC50=4 nM	23879463
THP1	Proliferation assay		Antiproliferative activity against human THP1 cells containing MLL-AF9, EC50=4 nM	23879463
HeLa	Function assay	72 hrs	Inhibition of DOT1L in human HeLa cells assessed as reduction in H3K79me2 level after 72 hrs by ELISA, IC50 = 0.007 μM.	28337327
MV4-11	Antiproliferative assay	6 hrs	Antiproliferative activity against human MV4-11 cells harboring MLL-AF4 treated for 6 hrs measured after 8 days by Celltiter-Glo reagent based assay, IC50 = 0.015 μM.	28337327
MOLM13	Function assay	72 hrs	Inhibition of DOT1L in human MOLM13 cells assessed as suppression of HoxA9 gene after 72 hrs by luciferase reporter gene assay, IC50 = 0.052 μM.	28337327
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	562.71	Formula	C₃₀H₄₂N₈O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1380288-87-8	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC(C)N(CC1C(C(C(O1)N2C=NC3=C(N=CN=C32)N)O)O)C4CC(C4)CCC5=NC6=C(N5)C=C(C=C6)C(C)(C)C

Solubility

In vitro
Batch:

DMSO : 100 mg/mL ( (177.71 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 25 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (8.89mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 30%PEG 300 2 5%Tween80 3 60% ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (8.89mM)	Taking the 1 mL working solution as an example, add 50 μL of 1000 mg/mL clarified DMSO stock solution to 300 μL PEG300, mix evenly to clarify; add 50 μL Tween-80 to the above system, mix evenly to clarify; Then continue to add 600 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	DOT1L ^[1] (Cell-free assay) 80 pM(Ki)
In vitro	EPZ-5676 reduces H3K79 dimethylation with a cellular IC50 of 2.6 nM in MV4-11 cells. EPZ-5676 treatment results in concentration- and time-dependent reduction of H3K79 methylation without effect on the methylation status of other histone sites, which leads to inhibition of key MLL target genes and selective, apoptotic cell killing in MLL-rearranged leukemia cells. EPZ-5676 inhibits proliferation of MLL-AF4 rearranged cell line MV4-11 with an IC50 of 9 nM.
In vivo	EPZ-5676 continuously intravenous infusion for 21 days to xenograft model of MLL-rearranged leukemia, leads to dose-dependent anti-tumor activity. At the highest dose of 70.5 mg/kg/day, complete tumor regressions are achieved with no regrowth for up to 32 days after the cessation of treatment. No significant weight loss or obvious toxicity is observed in rats treated with EPZ-5676 during efficacy study.
References	http://webcast.aacr.org/p/2013annual/182 https://ash.confex.com/ash/2012/webprogram/Paper48109.html https://pubmed.ncbi.nlm.nih.gov/23801631/

Applications

Methods	Biomarkers	Images	PMID
Western blot	p-p65 / p65 / NFATc1 CDK6 / BCL11A / Bcl-2 / RUNX1 / MEF2C / H3K79me3 / H4		29348610
Immunofluorescence	NFATc1		29348610

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT02141828	Completed	Leukemia\|Acute Myeloid Leukemia\|Acute Lymphocytic Leukemia\|Acute Leukemias	Epizyme Inc.\|Celgene Corporation\|Ipsen	May 2014	Phase 1
NCT01684150	Completed	Acute Myeloid Leukemia\|Acute Lymphoblastic Leukemia\|Myelodysplastic Syndrome\|Myeloproliferative Disorders	Epizyme Inc.\|Celgene\|Ipsen	September 2012	Phase 1

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Frequently Asked Questions

Question 1:
Is the vehicle 30% PEG400/0.5% Tween80/5% propylene glycol recommended for in vivo use?

Answer:
S7062 in 30% PEG400/0.5% Tween80/5% propylene glycol at 30 mg/ml is a suspension. For injection, 2% DMSO/30% PEG 300/5% Tween 80/ddH2O at 5 mg/ml is suitable.

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